Online Mendelian Inheritance in Man (OMIM) as a knowledgebase for human developmental disorders
Online Mendelian Inheritance in Man (OMIM) as a knowledgebase for human developmental disorders
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DOI：
10.1034/j.1399-0004.2000.570403.x
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发表时间：
2000-04-01
影响因子：
3.5
通讯作者：
Jabs, EW
中科院分区：
文献类型：
--
作者：
Boyadjiev, SA;Jabs, EW
在这篇综述中，我们总结了当前有关人类发育障碍的遗传信息（OMIM），OMIM目录人类表型和基因型以及相关的小鼠模型。在11 005多个遗传疾病和基因座中，我们发现至少有1231个具有已知基因突变的人类状况。我们搜索了在围产期期间存在结构缺陷的人类发育障碍，并确定了162条此类条目。我们通过表型特征（例如，骨骼发育异常，轴和侧向缺陷或眼部疾病）以及基因突变的类型（例如，编码转录因子，结构蛋白，酶或受体），34---八个条目具有带有基因突变的等位基因变体，从而导致不同的功能后果，从而改变了它们与它们的相互作用修饰基因。由于多个以上基因的功能冗余，在共同发育途径中相互作用，三十二个条目显示出遗传异质性。尽管许多不同类型的基因在发育障碍中被突变，但我们发现疾病基因是49个条目中的转录因子。小鼠模型可用于许多人类条件，其中大多数是继发于无效突变的。这些数据使我们能够开始阐明人类畸形分子发病机理所涉及的复杂发育途径。
In this review, we summarize the current genetic information on human developmental disorders found in Online Mendelian Inheritance in Man (OMIM), The OMIM catalogues human phenotypes and genotypes and relevant mouse models. Among the more than 11 005 genetic disorders and loci, we found at least 1231 human conditions with known gene mutations. We searched for human developmental disorders that present with structural defects during the perinatal period, and identified 162 such entries. We classified these entries by phenotypic features (e.g,, skeletal dysplasias, axis and laterality defects, or eye disorders) and by the type of gene mutated (e.g., genes coding for transcription factors, structural proteins, enzymes, or receptors), Thirty-eight entries have allelic variants with gene mutations causing different functional consequences, thereby altering their interactions with modifying genes. Thirty-two entries show genetic heterogeneity due to either functional redundancy of more than one gene or genes that interact in common developmental pathways. Although many different types of genes are mutated in developmental disorders, we found that the disease genes are transcription factors in 49 entries. Mouse models are available for many of the human conditions, with the majority of these mutants being secondary to null mutations. These data allow us to begin to elucidate the complex developmental pathways involved in the molecular pathogenesis of human malformations.